Triggering and modulation of the host-parasite interplay by Echinococcus multilocularis: a review (original) (raw)
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Protective immune mechanisms against the metacestode of Echinococcus multilocularis
Parasitology Today, 1995
Infection with the larval stage of the fox tapeworm Echinococcus multilocularis results in a life-threatening hepatic disease concerning humans and intermediate rodent hosts. Immunoepidemiological surveys provided information that a large proportion of infected individuals may demonstrate either constitutional resistance to early post-oncospheral development of the parasite or late resistance to disease by exhibiting an intrahepatic died-out parasite lesion. Similar events have been found in secondary infections of laboratory rodents. Dissection of humoral and cell-mediated immune responses in susceptible versus resistant individuals provides insight into immunological pathways associated with the different outcome of infection. Survival strategy of the metacestode obviously focuses on the crucial role played by the parasite laminated layer. This layer protects the metacestode from host effector mechanisms which can potentially kill the proliferating germinative compartments in case of resistant hosts. Bruno Gottstein and Richard Felleisen here discuss the need to search for more parameters discriminating between the different immune pathways in order to.find out (immunogenetic?) predispositions responsible for the respective phenomena.
Infection and Immunity, 2004
Echinococcus multilocularis metacestodes are fluid-filled, vesicle-like organisms, which are characterized by continuous asexual proliferation via external budding of daughter vesicles, predominantly in the livers of infected individuals. Tumor-like growth eventually leads to the disease alveolar echinococcosis (AE). We employed the monoclonal antibody (MAb) E492/G1, previously shown to be directed against a carbohydrate-rich, immunomodulatory fraction of Echinococcus granulosus, to characterize potentially related components in E. multilocularis. Immunofluorescence studies demonstrated that MAb E492/G1-reactive epitopes were found predominantly on the laminated layer and in the periphery of developing brood capsules. The respective molecules were continuously released into the exterior medium and were also found in the parasite vesicle fluid. The MAb E492/G1-reactive fraction in E. multilocularis, named Em492 antigen, was isolated by immunoaffinity chromatography. Em492 antigen had...
Medical Microbiology and Immunology, 2010
Alveolar echinococcosis, one of the most serious and life-threatening zoonoses in the world, is caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis. Mostly due to its accessibility to in vitro cultivation, this parasite has recently evolved into an experimental model system to study larval cestode development and associated host-parasite interaction mechanisms. Respective advances include the establishment of axenic in vitro cultivation systems for parasite larvae as well as culture systems by which the early development of metacestode vesicles from totipotent parasite stem cells can be reconstituted under controlled laboratory conditions. A series of evolutionarily conserved signalling molecules of the insulin, epidermal growth factor and transforming growth factor-b pathways that are able to functionally interact with corresponding host cytokines have been described in E. multilocularis and most likely play a crucial role in parasite development within the liver of the intermediate host. Furthermore, a whole genome sequencing project has been initiated by which a comprehensive picture on E. multilocularis cell-cell communication systems will be available in due time, including information on parasite cytokines that are secreted towards host tissue and thus might affect the immune response. In this article, an overview of our current picture on Echinococcus signalling systems will be given, and the potential to exploit these pathways as targets for anti-parasitic chemotherapy will be discussed. Keywords Signalling Á Chemotherapy Á Host-parasite interaction Á Stem cells Á Neoblasts This article is published as part of a Special Issue on Pathogen Variability and Host Response in Infectious Disease.
Immune Response to Echinococcus Multilocularis Infection in the Mouse Model : A Review
Echinococcus multilocularis is a cestode helminth which, along with E. granulosus, E. oligarthus and E. vogeli is a causative agent of hydatid disease in man. In the intermediate host (including man), cysts formed by the metacestode (larval stage) develop in the internal organs, causing functional impairment which often leads to the death of the host. In this review larval E. multilocularis infection in mice, the most popular experimental intermediate host, is examined, and the immune response to the organism is described in detail. Evidence is presented which suggests that cell-mediated immunity (eMl) plays a large role in suppression of larval growth. Congenitally athymic nude mice, and mice treated to remove thymocytes had high susceptibility to infection, while mice strains assessed as having high helper T lymphocyte function showed resistance to infection. The degree of antibody response shown by the host does not correlate with the susceptibility to E. multilocularis. Infection with E. multilocularis is accompanied by immunosuppression, manifested by inhibition of effector cell chemotaxis and receptor expression, suppressor macrophage and lymphocyte activity, decline in helper T-lymphocyte activity and immune-complex deposition.
Parasite, 2008
Parasitic helminths display highly complex life-cycles in which the establishment of adults or larvae within host target organs as well as the transition of one developmental stage to the following is influenced by host-derived factors. Due to its approachability concerning in vitro cultivation, the larval stage of the fox-tapeworm Echinococcus multilocularis has recently emerged as a model system to study the molecular nature of such host-derived stimuli and their influence on developmental control in the parasite. Data obtained so far indicate that cytokines which are used by the host for cell-cell communication can also be exploited by the parasite as clues to find suitable target organs. This involves direct interactions of evolutionary conserved signalling systems of the receptor tyrosine-and the receptor serine/threonine-kinase pathways of the parasite with corresponding host cytokines of the insulin-, the epidermal growth factor-, and the transforming growth factor-β-families. In the present article, we will briefly review in vitro cultivation approaches undertaken so far for E. multilocularis larvae as well as our current knowledge on the parasite's signalling systems and their interaction with host cytokines.
Immunomodulatory mechanisms during Echinococcus granulosus infection
Experimental Parasitology, 2008
The pathologic events that ensue after humans ingest the eggs of Echinococcus granulosus and continue while cystic echinococcosis develops, provide an excellent example illustrating the evasive strategies helminth parasites use to develop, progress and cause chronic disease. The hydatid cyst secretes and exposes numerous immunomodulatory molecules to the host's immune system. By characterizing these molecules we can understand the mechanisms that E. granulosus uses for increasing the efficiency and persistency of infection in the host. These molecules modulate both the innate and adaptive arms of the immune response and appear to target cellular and humoral responses. In this review, we discuss recent advances in the immunobiology of host-E. granulosus interactions that provide intriguing insights into the complex interplay between host and parasite that ultimately facilitates parasite survival.
Immunology, 2004
The role of specific B lymphocytes and T-cell populations in the control of experimental Echinococus multilocularis infection was studied in lMT, nude, T-cell receptor (TCR)-b-⁄-, major histocompatibility complex (MHC)-I-⁄and MHC-II-⁄mice. At 2 months postinfection, the parasite mass was more than 10 times higher in nude, TCR-b-⁄and MHC-II-⁄mice than in infected C57BL/6 wild-type (WT) mice, and these T-cell-deficient mice started to die of the high parasite load at this time-point. In contrast, MHC-I-⁄and lMT mice exhibited parasite growth rates similar to those found in WT controls. These findings clearly point to the major role that CD4 + ab + T cells play in limiting the E. multilocularis proliferation, while CD8 + T and B cells appeared to play a minor role in the control of parasite growth. In the absence of T cells, especially CD4 + or ab + T cells, the cellular immune response to infection was impaired, as documented by the lack of hepatic granuloma formation around the parasite and by a decreased splenocyte responsiveness to concanavalin A (Con A) and parasite antigen stimulation. Surprisingly, in T-cell-deficient mice, the ex vivo expression of interferon-c (IFN-c) and other inflammatory cytokines (except for interleukin-6) were increased in association with a high parasite load. Thus, the relative protection mediated by CD4 + ab + T cells against E. multilocularis infection seemed not be IFN-c dependent, but rather to rely on the effector's function of CD4 + ab + T cells. The local restriction of parasite germinal cell proliferation was reflected by a regulatory effect on the expression of 14-3-3 protein within the parasite tissue in T-cell-deficient mice. These results provide a strong indication that the CD4 + ab + T-cellmediated immune response contributes to the control of the parasite growth and to the regulation of production of the parasite 14-3-3 protein in metacestode tissues.
Infection and Immunity, 2001
Echinococcus multilocularis causes alveolar echinococcosis, one of the most lethal helminthic (accidental) infections in humans, as the life cycle predominantly includes wildlife rodents as intermediate hosts. The physical barrier between the proliferating parasitic metacestode and the host tissue is the acellular laminated layer (LL), which is characterized by its rich high-molecular-weight polysaccharide composition. Conversely to a crude protein-rich vesicular fluid antigen, a major carbohydrate antigen of the LL—the Em2(G11) antigen—did not stimulate murine T-cell proliferation in vitro. In fact, the persistent metacestode growth and antigenic stimulation induced a Th2 shift in vivo following conventional infection by intraperitoneal inoculation of 100 metacestode vesicles into C57/BL6 mice. Concurrently, the expression of Th1 cytokines (interleukin-2 and gamma interferon) remained persistently low until the late stage of chronic infection. In comparison to a recombinant protein...